Cancer Stem Cells
Advances in medical research these last decades permitted to importantly improve the existing cancer therapy strategies. In a parallel to the perpetual study and adaptation of the conventional therapeutic strategies including chemotherapy, radiotherapy, hormonal therapy and surgery, new cancer management approaches commonly called “targeted anti-cancer therapies” appeared and showed their efficiency and their interest in the medical world. These targeted therapies include monoclonal antibodies directed against tumor antigens such as trastuzumab (anti-Her2Neu), rituximab (anti-CD20) or bevacizumab (anti-VEGF), but also tyrosine kinase inhibitors (for example Imatinib, Erlotinib, Gefitinib), CDK inhibitors, etc. These new cancer treatment solutions largely improved the life of patients with increased survival rate and decreased side effects compared to more conventional strategies. However, these targeted therapy strategies also rapidly show limits, particularly due to resistance to said treatments, but also to the specificity of these targeted therapies, which are not efficient in every kind of cancers and patients. These resistance phenomena lead to treatment failure, appearance of metastases, relapses and recurrences.
Studies have shown that the root of these resistances might be the presence of cancer stem cells (CSC), a small subset of cancer cells that have the ability to self-renew and differentiate, and play a primordial role in cancer recalcitrance, recurrence and metastasis. Indeed, these cancer stem cells display relative resistance to cancer treatments, including radiation and chemotherapy. Furthermore, only a small amount of these cancer stem cells is sufficient to initiate a new tumor, and thus metastasis. Therefore, a direct targeting of these cancer stem cells may improve the efficacy of current cancer therapy strategies.
Cancer stem cells and associated mechanisms have thus been largely studied. Methods for identifying such cancer stem cells have been investigated, and few CSC markers were found. Unfortunately, there is still no antigen identified as CSC marker which is useful on many tumor types. Examples of currently used CSC markers include ALDH, CD133, CD44, CD24, CD166. Many different phenotypes have been identified as CSC phenotypes in different kind of cancers. Particularly, CD133, which is now widely used as a marker of cancer stem cells, appeared to be a good CSC marker in glioma.
Today, cell phenotype CD133+ is related to cancer stem cell in glioma; phenotype CD44+CD24−/low appears to be related to cancer stem cell in breast cancer; phenotype CD34+ appears to be related to cancer stem cell in leukemia, more particularly CD34+/CD38 is related to cancer stem cell in acute myeloid leukemia and phenotype CD34+/CD19+ appears to be related to cancer stem in acute lymphoid leukemia.
Unfortunately, most of known CSC markers are also expressed in some normal tissues. So, it would be of major interest to identify specific cancer markers that could be used as diagnostic and therapeutic CSC marker: they could be targeted for diagnosing, but also for treating cancers comprising cancer stem cells, herein called Cancer Stem Cells cancer (CSC cancer), without major side effects due to toxicity on healthy cells.